The present invention relates, in general, to plastic compositions and, in particular, to plastic compositions that may be used for medical containers, such as containers for the storage of blood and/or blood cells. The present invention also relates to methods for storing blood and/or blood cells in containers made from such compositions.
Whole blood is typically described as being made up of various cellular components such as red blood cells (RBCs), white blood cells (WBCs) and platelets, suspended in a liquid component, plasma. Each component plays a specific and important role in the human body. For example, platelets (together with clotting factors and other substances in the blood) are responsible for blood clotting. WBCs are primarily responsible for fighting disease. RBCs transport oxygen (O2) and carbon dioxide (CO2) to and from body tissues. The O2 and CO2 are carried by a protein called hemoglobin, which is found inside the RBC.
Blood and blood components are collected in a variety of ways. One of the most common blood collection techniques, and perhaps the most well known, is the manual collection of whole blood from healthy donors. This is usually performed at a local hospital, blood collection center or even a community center such as a local school or church as part of a blood collection drive. In the manual technique, a needle is inserted into the donor""s arm and blood is withdrawn from the donor through the needle and associated tubing. The withdrawn whole blood is collected in a sterile plastic collection container or pouch attached to the other end of the tubing. The collected xe2x80x9cunitxe2x80x9d of whole blood may then be transfused into a patient.
Alternatively, rather than transfusing an entire unit of whole blood, the collected whole blood may be separated into its various components, and the desired component may be transfused to a patient in need of that particular component. For example, separated RBCs may be administered to patients who have experienced rapid blood loss, or to improve the oxygen carrying capability of blood in patients suffering from anemia and the like. Platelets may be administered, for example, to cancer patients whose ability to produce platelets has been destroyed by chemotherapy and/or radiation treatment. Thus, separation of whole blood into individual components to be used as needed in different patients, results in more efficient usage of the available blood supply.
Briefly, manually collected whole blood may be separated into its components by first centrifuging the bag of collected whole blood to separate RBCs from the remaining components. Rotation of the centrifuge imparts a centrifugal force on the whole blood and causes the components of whole blood to sediment into layers or bands based on the densities of the components. Thus, the more dense (or xe2x80x9cheavierxe2x80x9d) components, such RBCs, are separated from the lighter components such as platelets and plasma. For example, centrifugation forces the RBCs to the bottom of the collection container, leaving most of the less dense platelets and plasma in a layer above the RBCs. The layers of blood components may be segregated from each other by either allowing the RBCs to drain out of the collection container and into a separate container, or by squeezing the collection container to express the remaining components (e.g. platelets and plasma) to a separate container. If additional separation of the platelets from plasma is desired, the remaining platelets and plasma may be centrifuged in similar fashion to provide xe2x80x9cplatelet-poor plasmaxe2x80x9d and platelet concentrate.
As an alternative to manual collection, whole blood may be separated and its components collected in an xe2x80x9cautomatedxe2x80x9d procedure or system. Automated blood collection systems or instruments typically include a separation device, such as a centrifuge, pumps and an associated disposable tubing set for moving blood, blood components and other fluids from the donor, to the centrifuge device and back to the donor. The disposable tubing set may also include containers which are placed inside the centrifuge device and where the blood is separated into its components. Examples of automated blood separation and collection instruments are the CS3000(copyright) Plus Blood Cell Separator and the Amicus(trademark) Separator, both made by Baxter Healthcare Corporation of Deerfield, Ill.
In an automated system, a needle (which is attached to tubing of the disposable tubing set) is inserted into the arm of the donor. Whole blood is then continuously or intermittently withdrawn from the donor and introduced into the separation container inside the rotating centrifuge where, under the influence of the centrifugal force (as described above), the desired components are separated from the undesired components. The desired component is collected in a collection container, while the undesired components may be returned (for example, by pumping) to the donor. The collected component may be transferred to a separate container for storage or, alternatively, may be stored in the collection container.
The containers for collection and/or storage of blood and blood components should be flexible, sterilizable and suitable for storage (and often extended storage) of blood and blood components. They are typically made of a plastic composition, two sheets of which are sealed together (in a facing arrangement) along their peripheries. Prior to introduction of the blood component, the container is sterilized by steam, gas or radiation sterilization. Like the disposable tubing sets described above, the containers are typically intended for one-time use and are disposed of after such use.
The plastic composition used in such containers typically includes a plastic resin that is suitable for contact with blood, such as polyvinyl chloride, polyolefin or polyester. The plastic composition may also include additives, for example, to stabilize the plastic composition during processing or during sterilization of the container, which may, at times, be carried out at high temperatures.
Unfortunately, exposure of certain plastic compositions to high temperatures, such as during extrusion of the plastic composition and/or during steam sterilization, may occasionally cause degradation of the plastic composition. Degradation, which is believed to be associated with a molecular breakdown of the polymer resins and other materials, may result in a weakening of the overall mechanical strength of the container. More particularly, degradation may result in a weakening of the peripheral seals and a reduction in the impact strength (i.e. ability of the container to withstand impact). Moreover, exposure to heat and/or even extended exposure to less severe environments may also cause undesirable and aesthetically unacceptable discoloration (e.g. yellowing) of the plastic material.
To prevent or reduce degradation and/or discoloration, inclusion of a small amount of certain additives can help stabilize the plastic material during high temperature heating and during exposure to certain other environments. As reported in U.S. Pat. No. 4,280,497, which is incorporated by reference herein, epoxodized oils, such as epodoxidized soy been oil and epoxodized linseed oil may be used as heat stabilizers. Also, as reported in Laermer et al. xe2x80x9cUse of Biological Antioxidants as Propylene stabilizersxe2x80x9d, Plastics and Rubber Processing and Applicants 14 (1990) 235-239 and Laermer et al. xe2x80x9cAlpha-Tocopherol (Vitamin E)xe2x80x94The Natural Antioxidant for Polyolefins xe2x80x9cJournal of Plastic Film and Sheeting, Vol. 8, July 1992 (both of which are also incorporated by reference), Vitamin E (which is a mixture of tocopherols and tocotrienols) is an antioxidant that can serve as a stabilizer during extrusion of polyolefins. Vitamin E as an antioxidant is preferred because, as reported in the 1992 article by Laermer, it is non-toxic and is xe2x80x9cgenerally regarded as safexe2x80x9d (GRAS) by the FDA.
Additives may also be combined with the plastic resin to enhance the storage of the blood and/or blood components. For example, a concern during the storage of platelets is the tendency of platelets to stick together and form platelet aggregates, which makes the platelets less suitable for transfusion to a patient. A concern during the storage of RBCs is that the membrane surrounding the RBC cell may rupture. The rupturing of the RBC membrane is commonly referred to as xe2x80x9chemolysisxe2x80x9d. The hemolysis of RBCs results in the release of hemoglobin, thus, impairing the RBC""s ability to transport O2 and CO2. These RBCs are less suitable for transfusion to a patient.
It has been observed that certain additives, such as Vitamin E may suppress hemolysis in red blood cells. As reported in U.S. Pat. No. 5,037,419, Vitamin E added directly to red blood cells, results in lower hemolysis. In addition, certain plasticizers (originally and still used as softeners for polyvinyl chloride), appear to have a beneficial effect on the viability of stored blood and/or red blood cells. It has been observed that red blood cells stored in plastic containers that include certain plasticizers experience a lower rate of hemolysis than RBCs stored in containers free of plasticizers. Thus, even for those materials that are not as rigid as PVC and are otherwise suitable for use in the storage of blood, including a sufficient amount of an additive, such as a plasticizer, may reduce the rate of hemolysis in the stored blood.
Several different plasticizers are suitable for use with PVC and non-PVC resins. For example, plasticizers from the family of phthalate esters, and in particular, di-2-ethylhexylphthalate (DEHP) have been used in combination with PVC resins. In addition, tri(2-ethylhexyl)trimellitate (TEHTM) has also been used with PVC resins. More recently, citrate esters have been used to plasticize PVC. PVC plasticized with citrate ester is described, for example, in U.S. Pat. Nos. 4,710,532, 4,789,700, 4,870,204, 4,883,905, 4,892,967, 4,931,583, 4,711,922 and 4,954,649, all of which are incorporated by reference herein. Non-PVC resins with citrate ester or TEHTM are described in U.S. Pat. Nos. 5,026,347, 5,100,401 and 5,167,657, all of which are assigned to the assignee of the present application and are incorporated by reference herein.
Of the above-identified plasticizers, the citrate esters and, in particular, n-butyryltri-n-hexyl citrate (sometimes abbreviated as BTHC) may be preferred because of the perceived ability of the human body to more easily metabolize citrate ester than, for example, DEHP. In addition, it is believed that, in certain circumstances, citrate esters may provide improved suppression of hemolysis as compared to DEHP and other plasticizers. However, BTHC is more expensive than TEHTM and DEHP and inclusion of BTHC increases the cost of making the container.
Blood storage containers which include some or all of the above identified resins and additives are disclosed in several patents. For example, the aforementioned U.S. Pat. No. 4,280,497 discloses a container for platelet storage that includes PVC, TEHTM plasticizer and epoxodized oils for heat stabilization. U.S. Pat. No. 5,037,419 discloses a plasticizer-free blood storage container made of a plastic material (such as polyester or polyolefin) where vitamin E is added to the stored blood so as to reduce hemolysis. U.S. Pat. No. 5,037,419 also contemplates, but does not describe in any detail, incorporating the Vitamin E into the plastic material directly.
The containers disclosed in the above-identified patents and elsewhere may work satisfactorily for storage of blood and/or some blood cells. Nonetheless, efforts to provide alternative formulations of resins and additives which, when combined, result in plastic compositions that are suitable for manufacture into blood storage containers have continued. It is desirable that such containers be capable of withstanding exposure to high temperatures and other environments without significant degradation and/or discoloration. It is also desirable that such containers be capable of enhancing the storage of blood or certain blood components by, for example, suppressing the rate of hemolysis in stored RBCs or reduce aggregation in stored platelets. As the blood storage containers are disposable and intended for one-time use, it is also desirable that such containers provide the above-described benefits at a relatively low cost.
There are several different aspects to the present invention which may be employed together or separately without departing from the present invention.
For example, the present invention is directed, in part, to a plastic composition that includes a plastic resin, Vitamin E and plasticizer. In one aspect of the present invention, the plastic resin may be polyvinyl chloride (xe2x80x9cPVCxe2x80x9d), while in another aspect of the present invention, the plastic resin may be a non-PVC such as polyolefin.
In another aspect, the present invention is directed to a plastic container made from a plastic composition that includes a plastic resin, Vitamin E and a plasticizer. In one aspect of the present invention, the plastic resin may be polyvinyl chloride while in another aspect of the present invention, the plastic resin may be a non-PVC resin such as polyolefin.
In another aspect, the present invention is directed to a method for storing blood cells. The method includes providing a container made of a plastic composition. The plastic composition includes a resin, Vitamin E and a plasticizer. The method includes introducing blood cells into the container and storing the blood cells therein.